Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0004153 (atherosclerosis)
77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Local immune responses are thought to play an important role in the development of atherosclerosis. Histological studies have shown that human atherosclerotic lesions contain T lymphocytes throughout all stages of development, many of which are in an activated state. A number of novel CC chemokines have been described recently, which are potent chemoattractants for lymphocytes: PARC (pulmonary and activation-regulated chemokine), ELC (EBI1-ligand chemokine), LARC (liver and activation-regulated chemokine), and SLC (secondary lymphoid-tissue chemokine). Using reverse transcriptase-polymerase chain reaction and in situ hybridization, we have found gene expression for PARC and ELC but not for LARC or SLC in human atherosclerotic plaques. Immunohistochemical staining of serial plaque sections with specific cell markers revealed highly different expression patterns of PARC and ELC. PARC mRNA was restricted to CD68+ macrophages (n = 14 of 18), whereas ELC mRNA was widely expressed by macrophages and intimal smooth muscle cells (SMC) in nearly all of the lesions examined (n = 12 of 14). ELC mRNA was also found to be expressed in the medial SMC wall of highly calcified plaques (n = 4). Very low levels of ELC mRNA expression could also be detected in normal mammary arteries but no mRNA expression for PARC was detected in these vessels (n = 4). In vitro, ELC mRNA was found to be up-regulated in aortic SMC stimulated with tumor necrosis factor-a and interferon-gamma but not in SMC stimulated with serum. Both PARC and ELC mRNA were expressed by monocyte-derived macrophages but not monocytes. The expression patterns of PARC and ELC mRNA in human atherosclerotic lesions suggest a potential role for these two recently described CC chemokines in attracting T lymphocytes into atherosclerotic lesions.
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PMID:Expression and cellular localization of the CC chemokines PARC and ELC in human atherosclerotic plaques. 1002 95

Common complications of cardiac transplantation include infection, rejection, accelerated coronary artery atherosclerosis, and lymphoproliferative disease. The authors reviewed radiographic and computed tomographic (CT) features of cardiac transplantation and its complications in a series of 232 patients (with 89 complications and 49 deaths). Normal postoperative findings in the first few weeks after surgery included enlarged cardiac silhouette, pneumomediastinum, pneumothorax, pneumopericardium, subcutaneous emphysema, and mediastinal widening. Infection was the most common complication, with pneumonia being the leading infectious condition (28 cases, with Aspergillus [n = 11] and cytomegalovirus [n = 10] being the most common pathogens) and the cause of death in seven cases. Although many cases of pulmonary infections occur in the first 3-4 months after surgery, in this series several cases developed up to 3 years afterward. Radiographic signs of acute rejection were nonspecific in the eight patients affected who died, and endomyocardial biopsy was used to confirm the suspected diagnosis. Accelerated atherosclerosis occurred in 13 patients between 10 months and 6.5 years after transplantation and led to death in eight. Lymphoproliferative disorders, which range from benign lymphoid hyperplasia to malignant lymphoma and which are the third leading cause of death beyond the immediate perioperative period in heart transplant recipients, developed in four patients who later died. Other complications related to endomyocardial biopsy and cardiothoracic surgery (i.e., pneumothorax, hemothorax, pneumomediastinum, mediastinitis, aortic dissection, aortic pseudoaneurysm, and pulmonary embolism) occurred in 31 cases and were diagnosed with radiography and CT.
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PMID:Imaging of cardiac transplantation complications. 1019 82

Malignant lymphoma infiltrating the abdominal aorta and resulting in an aortic aneurysm has never been documented. We report here a case of angiocentric T-cell lymphoma in a 33-year-old man who for months presented intermittent fever, splenomegaly, and an abdominal pulsatile mass. Angiography revealed extensive aneurysmal dilatation of the infrarenal abdominal aorta, bilateral iliac artery, and right common femoral artery. Splenic abscess and infected abdominal aortic aneurysm were initially suspected. An urgent splenectomy and aneurysmectomy with an aortic bifemoral bypass were performed. Pathological examination of the aortic aneurysm showed extensive necrosis, severe atherosclerosis, and lymphoma cell infiltration of the aortic wall. The lymphoid cells in the aorta and spleen were stained positive for CD45RO, CD56, and CD8, but negative for CD4 and CD19. Double-labeling immunohistochemistry and in situ hybridization using EBER1 for Epstein-Barr virus (EBV) revealed positive nuclear staining in the atypical T-lymphoid cells. This is the first definitive proof of peripheral T-cell lymphoma involving the abdominal aorta. Our evidence also supports that the EBV infection of T cells could be responsible for the atherosclerosis and hypertriglyceridemia, and the angiocentricity of the tumor cells apparently results in the presenting atherosclerotic aortic wall destruction, providing an additional causative concept for abdominal aortic aneurysm.
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PMID:Epstein-Barr virus-containing T-cell lymphoma and atherosclerotic abdominal aortic aneurysm in a young adult. 1049 49

The capability to cope with infectious agents and cancer cells resides not only in adaptive immune responses against specific antigens, mediated by T and B lymphocytes clonally distributed, but also in natural immune reactions. These innate defence mechanisms include chemotaxis, phagocytosis, natural cytotoxicity, cell interactions, and soluble mediators or cytokines. However, specific and natural immune mechanisms are always closely linked and interconnected, providing the primary defense against pathogens. The Authors discuss the main changes observed with advancing age in granulocytes and natural killer (NK) cell activity, in the expression and function of adhesion molecules, and in the pattern of cytokine production. Since phagocytic function is the primary mechanism through which the immune system eliminates most extracellular pathogenic microorganisms, analysis of this function is of clinical importance. Neutrophils from aged subjects often exhibit a diminished phagocytic capacity, as well as a depressed respiratory burst, notwithstanding an activated state. The activity of NK cells during aging has been studied extensively and different results have been reported. The most consistent data indicate an increase in cells with high NK activity with advancing age. Cells from healthy centenarians can efficiently kill target cells. This finding seems to suggest that innate immunity and in particular NK cell activity, is not heavily deteriorated with age. Conversely, a low NK activity is a predictor of impending morbidity. Immunosenescence is associated with increased expression of several cell adhesion molecules (CAM) resulting in an augmented capacity to adhere. Finally, also the cytokine network, responsible for differentiation, proliferation, and survival of lymphoid cells, undergoes complex changes with age. The main findings are a Th1 to Th2 cytokine production shift and an increased production of proinflammatory cytokines, which could explain many aspects of age-associated pathological events, such as atherosclerosis and osteoporosis.
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PMID:The immune system in the elderly: III. Innate immunity. 1058 Jun 37

With donor and recipient matched at the major histocompatibility complex (MHC) locus, peripheral lymphoid tissue transplantation can be carried out without producing a graft-versus-host reaction or graft-versus-host disease (GVHD), thus correcting profound T cell immunodeficiencies of neonatally thymectomized mice. This analysis set the stage for clinical application of bone marrow transplantation (BMT) to provide for the first time cure of a human disease. With successful BMT, we cured immunologic deficiencies of a patient with XL severe combined immunodeficiency; thereafter we were the first to employ BMT to cure aplastic anemia. BMT regularly corrects immune and hematologic deficiencies caused by fatal irradiation without producing GVHD if the bone marrow (BM) used for the transplants has been purged of postthymic T cells. Over two decades in conjunction with Ikehara et al., we have shown that lethal total body irradiation (TBI) plus allogeneic BMT prevents or cures many organ-specific and systemic experimental autoimmune diseases. Animal models successfully treated by BMT include type I diabetes in nonobese diabetes (NOD) mice, type II diabetes in insulin-insensitive, glucose intolerant, diabetes mellitus (KK/Ay) mice, and autoimmune lupus erythematosus (LE) and glomerulonephritis in New Zealand Black x New Zealand White first generation hybrid (NZB x NZW)F1 females. El-Badri extended Ildstad's original research showing a high frequency of survival with a normal functioning immune system after stable mixed chimerism is produced by mixed BMT in C57BL/6 (normal long-lived black strain) mice transplanted with T cell-depleted marrow (TCDM) from BALB/c ("normal" long-lived strain) allogeneic donors and C57BL/6 syngeneic donors. We showed that osteoblasts act as facilitator cells for allogeneic BMT and promote engraftment of allogeneic hematopoietic stem cells. Wang et al. then showed that the autoimmunities and fulminating renal disease of BXSB (C57BL x SB cross and selective lupus-like systemic autoimmunity) male mice was prevented and could be cured by transplantation using TCDM from both BALB/c (resistant) and BXSB (susceptible) strains given to BXSB recipients after lethal TBI. This treatment produced mixed BMT and a stable mixed chimerism, increased longevity, corrected all manifestations of autoimmunity, and cured fulminant glomerulonephritis in these recipients. These studies generated a new perspective on the potential usefulness of BM and stem cell transplants to cure major diseases that can possibly be treated by BMT. Mixed BMT from TCD BALB/c and BXSB mice cured autoimmunities and fulminant glomerulonephritis in BXSB mice. LE disease plus coronary vascular disease that occurs in (NZW x BXSB)F1 mice, along with idiopathic thrombocytopenic purpura, is also cured in lethally irradiated (NZW x BXSB)F1 mice by BMT from C57BL/6 donors. Furthermore, hemolytic anemia, autoimmune phenomena, and hyalinizing glomerular renal disease of New Zealand Black (NZB) mice were prevented or cured by stem cell transplants using purified stem cells from MHC-matched DBA/2 donors or NZB donors. Consequently, we reasoned that autoimmunities reside in stem cells. More recently, we found that transplants of both BM cells and bones can completely and permanently prevent otherwise highly resistant autoimmune diseases of MRL/lpr lpr mice and an autoimmune polyarthritis of NZB/Kn mice. Ildstad concluded that lethal preparative measures would not be acceptable for preparations to treat autoimmune diseases, so we now employ a gentle method for producing stable mixed chimerism described by Sharabi and Sachs to achieve mixed marrow transplantation and mixed hematopoietic chimerism. Other diseases we are approaching using this gentle manipulation include two forms of diabetes: insulin-dependent diabetes mellitus (IDDM) type I in NOD mice and non-insulin-dependent diabetes mellitus (NIDDM) type II in KK/Ay mice, atherosclerosis of apolipoprotein-E + kno
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PMID:Progress toward production of immunologic tolerance with no or minimal toxic immunosuppression for prevention of immunodeficiency and autoimmune diseases. 1083 46

Vascular-associated lymphoid tissue (VALT) consisting of accumulations of immunocompetent and antigen presenting cells has recently been recognised in the arterial wall. In this study, we investigated the involvement of VALT in immune responses in abdominal aortic aneurysms (AAAs). Tissue samples were collected during operations from 31 patients with atherosclerotic infrarenal abdominal aortic aneurysms ranging in diameters from 5 to 8 cm. The specimens were immediately frozen and examined using single and double immunohistochemical staining. T-cell subpopulations, B-cells, dendritic cells and macrophages were identified using cell type specific antibodies. Cell contacts were examined by electron microscopy. Most inflammatory infiltrates were found in the adventitia. T-cells were the predominant cell type in a majority of inflammatory infiltrates but in seventeen cases, typical lymphoid follicles with B-cells forming germinative centres were also observed. In eight cases, the lymphoid follicles aggregated in lymph node-like structures. Dendritic cells were present within all inflammatory infiltrates and contacted lymphocytes. The present observations show that in aortic aneurysm, VALT is involved in immune responses and its activation mostly occurs in the adventitia. The formation of lymphoid follicles and lymph node-like structures in the adventitia suggests that VALT might locally serve the entire complex of both cellular and humoral immune responses in the aneurysmal wall.
Atherosclerosis 2001 Jan
PMID:Vascular-associated lymphoid tissue (VALT) involvement in aortic aneurysm. 1113 78

Advanced atherosclerotic lesions often contain adventitial lymphoid infiltrates, which occasionally contain nodular aggregates resembling lymphoid follicles. The structural organization suggests that local maturation of B cells may take place at these sites, as described for the mucosa-associated lymphoid tissue (MALT). This concept was evaluated by studying the micro-anatomy and cellular composition of adventitial infiltrates associated with advanced atherosclerosis of the aorta. Sections of 22 atherosclerotic aortas were stained immunohistochemically for cellular markers characteristic for lymphoid follicles, such as HECA-452-positive endothelial cells, CD20-positive B cells, CD21-positive follicular dendritic cells, and CD68-positive macrophages. Ki-67 was used as a proliferation marker. The TUNEL technique was used to study the presence of apoptotic cells. Specimens containing MALT served as comparison and positive controls. Seven of the 22 atherosclerotic aortas contained adventitial infiltrates resembling lymphoid follicles. The organized nodular centres were composed of CD45RA+ B cells, follicular dendritic cells (CD21+), a few T lymphocytes (CD3+) and 'tingible body' macrophages (CD68+). A large number of cells were Ki-67-positive; apoptotic bodies were numerous and phagocytosed by macrophages. The parafollicular area contained CD45RO-positive T cells and HECA-452-positive vessels. Vessels elsewhere were always HECA-452-negative. Specimens with MALT showed similar features. This study reveals a close resemblance between adventitial lymphoid infiltrates in advanced atherosclerotic aortic disease and MALT, suggesting local generation of a humoral immune response, likely to be initiated by antigens released during a process of long-standing tissue injury and inflammation as part of advanced atherosclerosis.
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PMID:Adventitial infiltrates associated with advanced atherosclerotic plaques: structural organization suggests generation of local humoral immune responses. 1118 Jan 75

Chemokines are small basic proteins that are the major mediators of all leukocyte migration. There are at least 46 distinct chemokines, and 19 chemokine receptors, making it easily the largest cytokine family. Chemokines can be both beneficial and harmful, by either stimulating an appropriate immune response to microbial invasion, or by mediating pathologic tissue destruction in many types of human disease. Chemokines have been implicated in the tissue destruction seen in autoimmune diseases, atherosclerosis, allograft rejection, and neoplasia. Chemokines also play essential roles in normal lymphocyte trafficking to primary and secondary lymphoid organs for antigen presentation and lymphocyte maturation. Chemokines also regulate hematopoietic stem and progenitor cell homing and proliferation. Therefore, it is likely that chemokines will become important targets for pharmacologic intervention in a wide variety of human diseases in the future.
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PMID:Chemokine regulation of normal and pathologic immune responses. 1155 47

Recent data suggest that atherosclerosis might be a systemic (auto)immune reaction against heat shock protein 60, first occurring at notorious local predilection sites, i.e. the intima at arterial branching points. The local infiltration of mononuclear cells, mainly macrophage-derived foam cells, T cells and smooth-muscle cells in atheromatous plaques, have long been described. During the past few years, research has been concentrated on the early stages in the development of atherosclerosis, and on healthy arteries from young individuals unaffected by arterial disease. In this review, we summarize data characterizing pre-existing mononuclear cell infiltrations in healthy arteries from children and teenagers. These arterial accumulations at regions known to be predilection sites for the later development of atherosclerosis consist mostly of activated T cells, macrophages and dendritic cells, with only a few mast cells and virtually no B or natural killer cells. In analogy to the mucosa-associated lymphoid tissue, we termed these accumulations 'vascular-associated lymphoid tissue', and assumed a similar function as a local immunosurveillance system, monitoring the bloodstream for potentially harmful endogenous or exogenous antigens. In addition to the remarkable accumulation of mononuclear cells, the vascular-associated lymphoid tissue regions are characterized by a typical distribution of extracellular matrix proteins: collagen type I, collagen type III, fibronectin and tenascin are expressed preferentially in the vascular-associated lymphoid tissue region, whereas collagen type IV, collagen type V, collagen type VI and laminin show a homogenous distribution throughout all regions of the intima. Vascular adhesion molecules type 1, intercellular adhesion molecules type 1 and P-selectin are already present on the healthy endothelial cells of young children. Interactions between adhesion molecules, extracellular matrix components and cellular elements of the vascular-associated lymphoid tissue may provide the basis for the cellular accumulations in the vascular-associated lymphoid tissue regions and the possible development of atherosclerotic lesions later in life.
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PMID:The vascular-associated lymphoid tissue: a new site of local immunity. 1156 Nov 75

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study gave insight into the correlation between the classical risk factors for atherosclerosis development, such as hypercholesterolemia, hyperglycemia, high blood pressure and smoking in young Americans. We now present immunohistochemical data showing that immunological-inflammatory signs represent the first step towards atherosclerosis development in the arteries of young adults. In previous publications, we coined the term 'vascular-associated lymphoid tissue' (VALT) for the accumulation of mononuclear cells at regions of the arterial wall in healthy children and adolescents that are predisposed to the development of atherosclerotic lesions later in life if risk factors are present. In the present communication, we intended to close the gap between data from atherosclerotic arteries and those of healthy young children studied previously by our group. The PDAY-study comprising 15-34-year-old Americans who had no clinical symptoms of cardiovascular diseases offered a good basis for our intention. We document that inflammatory activity was found in all specimens, represented by activated T-lymphocytes, dendritic cells, macrophages and aberrant MHC class II expression in the intima. We therefore demonstrated that immunological-inflammatory cells are present in the earliest stages of atherogenesis in 15-34-year-old subjects, arguing in favour of an initiating role of the immune system in atherosclerosis development.
Atherosclerosis 2002 Feb
PMID:Early inflammatory-immunological lesions in juvenile atherosclerosis from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study. 1184 69


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